protocol_id stringclasses 263
values | section_number stringlengths 1 12 | title stringlengths 1 1.88k | content stringlengths 0 866k | merged_titles listlengths 0 491 |
|---|---|---|---|---|
NCT04603495 | 6.5.4.2 | Re-escalation of Pelabresib/Placebo after Dose Reduction for Toxicity | 6.5.4.2. Re-escalation of Pelabresib/Placebo after Dose Reduction for Toxicity Patients who have had a dose reduction or dose hold of ruxolitinib or pelabresib/placebo because of an AE may increase the dose of pelabresib/placebo only if all of the following criteria are met: - The ruxolitinib dose has reached at least ... | [] |
NCT04603495 | 6.6 | Crossover Period | 6.6. Crossover Period Patients who have enrolled in the control group (i.e., treated with placebo + ruxolitinib) and have progressive disease after 24 weeks of treatment by radiological parameters may be crossed over to receive the experimental treatment of pelabresib + ruxolitinib. The following sections detail the de... | [] |
NCT04603495 | 6.6.1 | Crossover Design | 6.6.1. Crossover Design All patients who have progressive disease at any time will be required to discontinue the doubleblind- study treatment. Patients in the control group who have progressive disease due to splenomegaly (i.e., defined as enlargement of spleen volume by MRI or CT scan of ≥25% compared to the baseline... | [] |
NCT04603495 | 6.6.2 | Operational Considerations for Crossover | 6.6.2. Operational Considerations for Crossover At the time of crossover consideration, patients will be fully informed of the crossover treatment option within the study, as well as all available treatment options, including approved and investigational, outside of the study as part of re-consenting (Section [10.1.3\)... | [] |
NCT04603495 | 6.6.3 | Clinical Considerations for Crossover | 6.6.3. Clinical Considerations for Crossover
Eligibility Patients must meet the following inclusion criteria at the time of crossover being considered: - Splenic progression (>25% increase from baseline) assessed by central review within 28 days of initiating crossover - Have acceptable laboratory assessments obtained... | [
"Eligibility",
"Starting Doses and Uptitration Criteria",
"Dose Modifications",
"Assessments and Procedures"
] |
NCT04603495 | 6.6.4 | Statistical Considerations for Crossover | 6.6.4. Statistical Considerations for Crossover The crossover design will have no impact on the analysis of the primary (splenic response at Week 24) and key secondary (TSS response at Week 24) endpoints, as the crossover will only occur after the Week 24 assessments. Since spleen volume will be independently assessed ... | [] |
NCT04603495 | 6.7 | Supportive Care | 6.7. Supportive Care | [] |
NCT04603495 | 6.7.1 | Nausea and/or Vomiting | 6.7.1. Nausea and/or Vomiting | [] |
NCT04603495 | 6.7.1.1 | Prophylaxis for Nausea and/or Vomiting | 6.7.1.1. Prophylaxis for Nausea and/or Vomiting It is strongly recommended that patients receive oral nausea/vomiting prophylaxis for the first 2 cycles prior to doses of pelabresib/placebo. To this end, patients are recommended to receive ondansetron 4 to 8 mg QD PO (or a comparable antiemetic) 30 minutes before each ... | [] |
NCT04603495 | 6.7.1.2 | Management of Nausea and/or Vomiting | 6.7.1.2. Management of Nausea and/or Vomiting If a patient still experiences ≥ Grade 3 nausea/vomiting despite prophylaxis, consider following the NCCN guidelines or local applicable guidelines for the treatment of nausea/vomiting. From the Phase 2 experience, separation of pelabresib/placebo and ruxolitinib intake by ... | [] |
NCT04603495 | 6.7.2 | Management of Diarrhea | 6.7.2. Management of Diarrhea Patients who develop diarrhea should be treated with anti-diarrhea medication, such as loperamide, as per standards of care and/or institutional guidelines. Fluid intake should be maintained to avoid dehydration. Patients who develop significant new or worsening diarrhea during study treat... | [] |
NCT04603495 | 6.7.3 | Management of Rash | 6.7.3. Management of Rash Patients who develop rash should be treated with supportive care as follows: for Grade 1, provide an oral antihistamine (e.g., hydroxyzine) as needed and a topical corticosteroid cream as needed. For ≥ Grade 2, begin a course of oral prednisone 10 mg once daily for 1 week, followed by 5 mg onc... | [] |
NCT04603495 | 6.7.4 | Management of Ruxolitinib Discontinuation Syndrome (RDS) | 6.7.4. Management of Ruxolitinib Discontinuation Syndrome (RDS) Instances of severe adverse events occurring subsequent to ruxolitinib withdrawal have been reported in the literature. RDS includes clinical manifestations ranging from acute relapse of disease-related symptoms, rapid spleen volume enlargement, and worsen... | [] |
NCT04603495 | 6.8 | Concomitant Therapy | 6.8. Concomitant Therapy The following concomitant medications are prohibited during study treatment (and some require a washout period, as noted below): - Systemic anti-neoplastic medications, including hydroxyurea and anagrelide. Patients should discontinue hydroxyurea or anagrelide 24 hours prior to the first dose o... | [] |
NCT04603495 | 6.9 | Contraception | 6.9. Contraception Instructions on the use of effective contraceptive measures during and after study treatment follow the current recommendations of the HMA/CTFG and EMA. | [] |
NCT04603495 | 6.9.1 | Female Patients | 6.9.1. Female Patients Female patients of childbearing potential (WOCBP) are required to use at least one highly effective method of contraception (preferably low user dependency contraception methods, in particular when contraception is introduced as a result of participation in a clinical study) while receiving study... | [] |
NCT04603495 | 6.9.2 | Male Patients | 6.9.2. Male Patients Due to the potential risk of genotoxicity based on pre-clinical data, male patients regardless of fertility must use a condom during sexual intercourse while receiving study drug and for 94 days after the last dose of study drug. | [] |
NCT04603495 | 6.9.3 | Female Partners (WOCBP, Non-pregnant) of Male Patients | 6.9.3. Female Partners (WOCBP, Non-pregnant) of Male Patients It is highly recommended for female (WOCBP, non-pregnant) partners of male patients to use additional highly effective contraception methods (listed above) in combination with male condom. | [] |
NCT04603495 | 6.9.4 | Oocyte and Sperm Donation | 6.9.4. Oocyte and Sperm Donation Donation of oocytes by the female patients during the study and for 184 days after the last dose of study drug is not allowed. Donation of sperm by the male patients during the study and for 94 days after the last dose of study drug is not allowed. | [] |
NCT04603495 | 7 | DISCONTINUATION OF STUDY DRUG AND PATIENT WITHDRAWAL FROM THE STUDY | 7. DISCONTINUATION OF STUDY DRUG AND PATIENT WITHDRAWAL FROM THE STUDY | [] |
NCT04603495 | 7.1 | Discontinuation of Study Drug | 7.1. Discontinuation of Study Drug Study treatment is to be permanently discontinued for patients meeting any of the following criteria: - Patients who were randomized, but not able to start treatment within 28 days of the start of screening. Study treatment is defined as the combination of pelabresib + ruxolitinib or ... | [] |
NCT04603495 | 7.2 | Patient Withdrawal from the Study Treatment/Study | 7.2. Patient Withdrawal from the Study Treatment/Study A patient may withdraw from the study treatment/study at any time at his/her own request or may be withdrawn at any time at the discretion of the Investigator for safety, behavioral, compliance, or administrative reasons. This is expected to be uncommon. Patients h... | [] |
NCT04603495 | 7.3 | Lost to Follow-up | 7.3. Lost to Follow-up A patient will be considered lost to follow-up if he or she repeatedly fails to return for scheduled visits and is unable to be contacted by the study site. The following actions must be taken if a patient fails to return to the clinic for a required study visit: • The site must attempt to contac... | [] |
NCT04603495 | 8 | STUDY ASSESSMENTS AND PROCEDURES | 8. STUDY ASSESSMENTS AND PROCEDURES Study procedures and their timing are summarized in the SoA (Section [1.3\)](#page-16-0). Protocol waivers or exemptions are not allowed. Adherence to the study design requirements, including those specified in the SoA, is essential and required for study conduct. All screening evalu... | [] |
NCT04603495 | 8.1 | Demographics and Medical History Assessments | 8.1. Demographics and Medical History Assessments Patient demographics will be documented during screening and will include patient's year of birth, gender, ethnicity, and race. The patient will have a complete medical history taken to include all past and ongoing medical conditions. The medical history will also inclu... | [] |
NCT04603495 | 8.2 | Efficacy Assessments | 8.2. Efficacy Assessments | [] |
NCT04603495 | 8.2.1 | Disease Status Assessments | 8.2.1. Disease Status Assessments The patient's disease status will be evaluated by measurement of peripheral blood counts, history/documentation of transfusion requirements, MF-associated symptoms, spleen size by palpation and by MRI/CT, and grading of bone marrow fibrosis as assessed by bone marrow biopsy. Disease st... | [] |
NCT04603495 | 8.2.2 | Patient-Reported Outcomes | 8.2.2. Patient-Reported Outcomes The MFSAF assessment (version 4.0) should be completed electronically every day irrespective of any cycle delays starting from at least 7 days prior to randomization until 12 weeks after the end of treatment. The MFSAF asks patients to rate the severity of each of seven symptoms (fatigu... | [] |
NCT04603495 | 8.3 | Safety Assessments | 8.3. Safety Assessments Any patient who receives treatment on this protocol will be evaluable for toxicity. Each patient will be assessed periodically for the development of any toxicity according to the SoA (Section [1.3\)](#page-16-0). Toxicity will be assessed according to the NCI CTCAE, v5.0. The Investigator shoul... | [] |
NCT04603495 | 8.3.1 | Concomitant Medications | 8.3.1. Concomitant Medications Any other permitted medication or vaccine (including over-the-counter or prescription medicines, vitamins, and/or herbal supplements) that the patient is receiving at the time of enrollment or receives during the study must be recorded along with: - Reason for use - Dates of administratio... | [] |
NCT04603495 | 8.3.2 | Physical Examinations, Including Spleen Examination, and Vital Signs | 8.3.2. Physical Examinations, Including Spleen Examination, and Vital Signs A complete physical examination will be performed at the time points noted in the SoA (Section [1.3\)](#page-16-0) and will include general appearance, HEENT, neck, cardiovascular, thorax/lungs, breasts, abdomen, genitourinary, musculoskeletal,... | [] |
NCT04603495 | 8.3.3 | ECOG Performance Status | 8.3.3. ECOG Performance Status ECOG performance status will be assessed at the time points noted in the SoA (Section [1.3\)](#page-16-0). ECOG assessment should be conducted ≤ 72 hours before the start of each scheduled cycle. | [] |
NCT04603495 | 8.3.4 | Electrocardiograms | 8.3.4. Electrocardiograms A single 12-lead ECG will be obtained at the time points noted in the SoA (Section [1.3\)](#page-16-0) at least 1 hour after dosing of study drug. Additional unscheduled ECGs should be performed per investigator judgment (e.g., in the event of ≥ Grade 3 plasma potassium increase [see Section [... | [] |
NCT04603495 | 8.3.5 | Clinical Safety Laboratory Assessments | 8.3.5. Clinical Safety Laboratory Assessments The laboratory assessments to be collected during the study at the time points noted in the SoA (Section [1.3\)](#page-16-0) are detailed in Section [10.2.](#page-81-1) These assessments include hematology, clinical chemistry, coagulation parameters, serum lipids, HbA1c, an... | [] |
NCT04603495 | 8.4 | AEs and SAEs | 8.4. AEs and SAEs The Investigator and any qualified designees are responsible for detecting, documenting, and recording events that meet the definition of an AE or SAE throughout the study and remain responsible for following up AEs that are considered at least possibly related to the study drug or study procedures, o... | [] |
NCT04603495 | 8.4.1 | AE and SAE Definitions | 8.4.1. AE and SAE Definitions An AE is any untoward medical occurrence in a patient administered a study drug that does not necessarily have a causal relationship with the study drug. An AE can therefore be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associ... | [] |
NCT04603495 | 8.4.2 | Time Period and Frequency for Collecting AE and SAE Information | 8.4.2. Time Period and Frequency for Collecting AE and SAE Information All AEs, both non-serious and serious, and deaths will be collected and recorded on the eCRF from the signing of the ICF through 30 (±3) days after administration of the last dose of pelabresib/placebo or the start of alternative (off-study) treatme... | [] |
NCT04603495 | 8.4.3 | Method of Detecting AEs and SAEs | 8.4.3. Method of Detecting AEs and SAEs All AEs spontaneously reported by the patient and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded in the appropriate section of the eCRF. When possible, signs and symptoms in... | [] |
NCT04603495 | 8.4.4 | Follow-up of AEs and SAEs | 8.4.4. Follow-up of AEs and SAEs After the initial AE/SAE report, the Investigator is required to proactively follow each patient at subsequent visits/contacts. All AEs considered at least possibly related to study drug and all SAEs that occur during the reporting period (during the course of the study and designated s... | [] |
NCT04603495 | 8.4.5 | Regulatory Reporting Requirements for SAEs | 8.4.5. Regulatory Reporting Requirements for SAEs Prompt notification by the investigator to the Sponsor or its designee (Safety CRO) of a SAE is essential so that legal obligations and ethical responsibilities towards the safety of patients and the safety of a study intervention under clinical investigation are met. T... | [] |
NCT04603495 | 8.4.6 | Pregnancy | 8.4.6. Pregnancy A positive urine pregnancy test requires immediate interruption of study drug until serum HCG is performed and found to be negative. If a female patient or a female partner of a male patient becomes pregnant or suspects pregnancy while participating in this study and during the followup contraception p... | [] |
NCT04603495 | 8.4.7 | Disease-Related Events and/or Disease-Related Outcomes | 8.4.7. Disease-Related Events and/or Disease-Related Outcomes The FDA guidance on safety reporting directs Sponsors to specify AEs that may be common in the study population and as such may not meet the guidance criteria for expedited reporting. Per the guidance, a limited number of occurrences of an AE in a study popu... | [] |
NCT04603495 | 8.4.8 | Adverse Events of Special Interest (AESIs) | 8.4.8. Adverse Events of Special Interest (AESIs) Selected non-serious and serious adverse events are also known as AESIs and must be reported within 24 hours to the Safety CRO. For the time period beginning when the ICF is signed through 30 days after administration of the last dose of pelabresib/placebo or the start ... | [
"AESIs for this trial include:"
] |
NCT04603495 | 8.5 | Treatment of Overdose | 8.5. Treatment of Overdose For this study, any dose of study drug greater than the recommended Phase 2 dose of pelabresib (225 mg QD; Section [4.3\)](#page-30-0) per day or greater than 50 mg (25 mg BID) of ruxolitinib per day will be considered an overdose. The Sponsor does not recommend specific treatment for an over... | [] |
NCT04603495 | 8.6 | Pharmacokinetics | 8.6. Pharmacokinetics Blood samples (approximately 4 mL per sample) will be collected for the determination of pelabresib and its metabolites M542/M544 as well as ruxolitinib concentrations in plasma. The specific collection timepoints are listed in [Table 5.](#page-68-3) When PK sampling coincides with 12-lead ECGs, b... | [] |
NCT04603495 | 8.7 | Pharmacodynamics | 8.7. Pharmacodynamics The following biomarker assessments will be completed in all patients. [Table 6](#page-69-1) outlines the pharmacodynamic sampling schedule. Additional details regarding the collection, handling and shipping of samples are provided in the laboratory manual. All blood and bone marrow samples collec... | [
"Bone marrow biopsy evaluation",
"Circulating analytes evaluation",
"Mutant allele burden evaluation"
] |
NCT04603495 | 9 | STATISTICAL CONSIDERATIONS | 9. STATISTICAL CONSIDERATIONS A more technical and detailed description of the statistical methods will be provided in the SAP. | [] |
NCT04603495 | 9.1 | Study Endpoints | 9.1. Study Endpoints | [] |
NCT04603495 | 9.1.1 | Primary Endpoint | 9.1.1. Primary Endpoint The primary endpoint of the study is splenic response, defined as a ≥ 35% reduction from baseline in spleen volume as measured by MRI or CT and assessed by central radiology read, at Week 24. | [] |
NCT04603495 | 9.1.2 | Key Secondary Endpoints | 9.1.2. Key Secondary Endpoints The key secondary endpoints of the study are the absolute change in TSS at Week 24 compared to baseline and TSS response, defined as a ≥ 50% decrease from baseline in TSS as measured by the MFSAF v4.0, at Week 24. Baseline TSS is calculated as the average of non-missing daily total sympto... | [] |
NCT04603495 | 9.1.3 | Secondary Endpoints | 9.1.3. Secondary Endpoints The following secondary endpoints will be calculated and summarized for each treatment group: - Percent change in TSS at Week 24 compared to baseline - Improvement in bone marrow fibrosis by at least 1 grade at Week 24 compared to baseline - Splenic response at Week 48, defined as a ≥35% redu... | [] |
NCT04603495 | 9.1.4 | Exploratory Endpoints | 9.1.4. Exploratory Endpoints The following exploratory endpoints may be calculated and summarized for each treatment group: - Percent change in splenic volume at Week 24 - RBC transfusion dependence, defined as ≥ 6 units of RBC transfusion during the prior 12 weeks, at Week 24 - Hemoglobin response, defined as a ≥ 1.5 ... | [] |
NCT04603495 | 9.2 | Analysis Populations | 9.2. Analysis Populations The analysis populations for this study are defined in [Table](#page-73-4) 7. Table 7: Analysis Populations | Population | Description | |--------------|---------------------------------------------------------------------------------------------------------------------------------------------... | [] |
NCT04603495 | 9.3 | Statistical Analyses | 9.3. Statistical Analyses | [] |
NCT04603495 | 9.3.1 | General Considerations | 9.3.1. General Considerations Continuous variables will be summarized using descriptive statistics (n, mean, standard deviation, median, minimum, and maximum). Categorical variables will be summarized showing the number and percentage (n, %) of patients within each classification. Two-sided 95% confidence intervals wil... | [] |
NCT04603495 | 9.3.2 | Demographic and Baseline Characteristics | 9.3.2. Demographic and Baseline Characteristics Patient demographics (e.g., age, sex, race, ethnicity) and physical characteristics (e.g., height, weight, BMI) will be summarized by treatment group. Baseline disease characteristics (e.g., MF subtype, risk status, mutational profile, ECOG performance score, RBC transfus... | [] |
NCT04603495 | 9.3.3 | Efficacy Analyses | 9.3.3. Efficacy Analyses | [] |
NCT04603495 | 9.3.3.1 | Analysis of Primary and Key Secondary Endpoints | 9.3.3.1. Analysis of Primary and Key Secondary Endpoints The primary analysis will take place after all randomized patients have either completed their Week 24 visit or been prematurely discontinued. By this time, it is expected that at least 50% of the randomized patients will have completed their Week 36 visit. Until... | [
"Multiplicity and Type I Error Control",
"Handling of Missing Data"
] |
NCT04603495 | 9.3.3.2 | Analysis of Other Efficacy Endpoints | 9.3.3.2. Analysis of Other Efficacy Endpoints Details of the analyses of other secondary endpoints and exploratory endpoints will be provided in the SAP. | [] |
NCT04603495 | 9.3.4 | Safety Analyses | 9.3.4. Safety Analyses All safety analyses will be conducted using the Safety Population. Safety will be evaluated by incidence of TEAEs and by changes from baseline vital signs, ECGs, and clinical laboratory values. Exposure to study drug and reasons for discontinuation will also be summarized. Treatment-emergent AEs ... | [] |
NCT04603495 | 9.3.5 | PK/PD Analyses | 9.3.5. PK/PD Analyses PK data evaluation will be performed using an integrated population PK approach. PK/PD data evaluation will be provided in a separate document. | [] |
NCT04603495 | 9.4 | Sample Size Determination | 9.4. Sample Size Determination Assuming a splenic response rate of 62% in the experimental group and 29% in the control group, and assuming a TSS response rate of 57% in the experimental group and 42.2% in the control group [\(Mascarenhas et al., 2019;](#page-100-4) [Mesa et al., 2017\)](#page-100-9), if the sequential... | [] |
NCT04603495 | 10 | SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS | 10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS | [] |
NCT04603495 | 10.1 | Appendix 1: Regulatory, Ethical, and Study Oversight Considerations | 10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations | [] |
NCT04603495 | 10.1.1 | Regulatory and Ethical Considerations | 10.1.1. Regulatory and Ethical Considerations The study will be conducted in accordance with the ICH GCP and the appropriate regulatory requirement(s). The clinical study can only begin once approval from all required authorities has been received. The Investigator will be thoroughly familiar with the appropriate use o... | [] |
NCT04603495 | 10.1.2 | Financial Disclosure | 10.1.2. Financial Disclosure Investigators and sub-investigators will provide the Sponsor with sufficient, accurate financial information as requested to allow the Sponsor to submit complete and accurate financial certification or disclosure statements to the appropriate regulatory authorities. Investigators are respon... | [] |
NCT04603495 | 10.1.3 | Informed Consent Process | 10.1.3. Informed Consent Process After the study has been fully explained, written informed consent will be obtained from either the patient or his/her guardian or legal representative prior to study participation. The method of obtaining and documenting the informed consent and the contents of the consent will comply ... | [] |
NCT04603495 | 10.1.4 | Data Protection | 10.1.4. Data Protection In order to maintain patient privacy, all eCRFs, study drug accountability records, study reports and communications will identify the patient by the assigned patient number. The Investigator will grant monitor(s) and auditor(s) from the Sponsor or its designee and regulatory authority(ies) acce... | [] |
NCT04603495 | 10.1.5 | Use of Information | 10.1.5. Use of Information All information regarding pelabresib supplied by or on behalf of the Sponsor to the Investigator is privileged and confidential information. The Investigator agrees to use this information to accomplish the study and will not use it for other purposes without consent from the Sponsor. It is u... | [] |
NCT04603495 | 10.1.6 | Dissemination of Clinical Study Data | 10.1.6. Dissemination of Clinical Study Data Upon completion of the clinical trial and evaluation of results by the Sponsor, hospital or institution and/or Investigator may publish or disclose the clinical trial results pursuant to the terms contained in the applicable Clinical Trial Agreement. Study information and ta... | [] |
NCT04603495 | 10.1.7 | Data Quality Assurance | 10.1.7. Data Quality Assurance The Sponsor or its designated representative will conduct a study site visit to verify the qualifications of each Investigator, inspect trial site facilities, and inform the Investigator of responsibilities and procedures for ensuring adequate and correct study documentation. The Investig... | [] |
NCT04603495 | 10.1.8 | Source Documents | 10.1.8. Source Documents Source documents provide evidence for the existence of the patient and substantiate the integrity of the data collected. Source documents are filed at the Investigator's site. Data entered in the eCRF that are transcribed from source documents must be consistent with the source documents or the... | [] |
NCT04603495 | 10.1.9 | Study Monitoring | 10.1.9. Study Monitoring Monitoring and auditing procedures developed or approved by the Sponsor will be followed, in order to comply with GCP guidelines. On-site and remote review of the eCRFs for completeness and clarity, cross-checking with source documents, and clarification of administrative matters will be perfor... | [] |
NCT04603495 | 10.1.10 | Investigator and Site Responsibility for Drug Accountability | 10.1.10. Investigator and Site Responsibility for Drug Accountability Accountability for the study drug at the study site is the responsibility of the Investigator. The Investigator will ensure that the study drug is used only in accordance with this protocol. Where allowed, the Investigator may choose to assign some o... | [] |
NCT04603495 | 10.1.11 | Study and Site Start and Closure | 10.1.11. Study and Site Start and Closure The study start date is the date on which the clinical study will be open for recruitment of patients. Recruitment and enrollment strategies for this study may include recruitment from the Investigators' local practices or referrals from other physicians. If advertisements beco... | [] |
NCT04603495 | 10.1.12 | Publication Policy | 10.1.12. Publication Policy The results of this study may be published or presented at scientific meetings. If this is foreseen, the Investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission and to comply with the applicable provisions of any clinical trial agreement. This allows the S... | [] |
NCT04603495 | 10.2 | Appendix 2: Clinical Laboratory Tests | 10.2. Appendix 2: Clinical Laboratory Tests - The tests detailed in the table below will be performed by the local laboratory. - Protocol-specific requirements for inclusion or exclusion of patients are detailed in Section [5](#page-32-1) of the protocol. - The results of each test must be entered into the eCRF. Invest... | [] |
NCT04603495 | 10.3 | Appendix 3: Procedures for Recording, Evaluating, and Follow-up of AEs | 10.3. Appendix 3: Procedures for Recording, Evaluating, and Follow-up of AEs
AE and SAE Recording - When an AE/SAE occurs, it is the responsibility of the Investigator to review all available documentation (e.g., hospital progress notes, laboratory reports, and diagnostics reports) related to the event. - The Investig... | [
"AE and SAE Recording",
"Assessment of Intensity",
"Assessment of Seriousness",
"Assessment of Causality",
"Follow-up of AEs and SAEs"
] |
NCT04603495 | 10.4 | Appendix 4: WHO Diagnostic Criteria for MF | 10.4. Appendix 4: WHO Diagnostic Criteria for MF
WHO criteria for overt PMF\\
Major Criteria - 1. Presence of megakaryocytic proliferation and atypia, accompanied by either reticulin and/or collagen fibrosis grades 2 or 3\ - 2. Not meeting WHO criteria for ET, PV, BCR-ABL1+ CML, myelodysplastic syndromes, or other my... | [
"WHO criteria for overt PMF\\\\",
"Major Criteria",
"Minor Criteria"
] |
NCT04603495 | 10.5 | Appendix 5: DIPSS | 10.5. Appendix 5: DIPSS The DIPSS score is calculated based on the following 5 variables: - a. Age >65: 1 point - b. Leukocyte count >25 × 109 /L: 1 point - c. Hemoglobin \ Weight loss >10% of the baseline value in the year preceding MF diagnosis, and/or unexplained fever or excessive sweats persisting for more than on... | [] |
NCT04603495 | 10.7 | Appendix 7: IWG-MRT Response Criteria | 10.7. Appendix 7: IWG-MRT Response Criteria | Category | Required criteria(for all response categories, benefit must last for ≥12 wk to qualify as a response) | |----------|---------------------------------------------------------------------------------------------------------------------------------------------------... | [] |
NCT04603495 | 10.8 | Appendix 8: Strong CYP3A4 Inducers or Inhibitors | 10.8. Appendix 8: Strong CYP3A4 Inducers or Inhibitors The following lists were compiled from these resources and is not considered an all-inclusive list: - FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. See: https://www.fda.gov/drugs/developmentapprovalprocess/developmentreso... | [] |
NCT04603495 | 10.9 | Appendix 9: Study Conduct in Unforeseen Circumstances | 10.9. Appendix 9: Study Conduct in Unforeseen Circumstances
Summary: This appendix may be utilized by clinical trial sites during unforeseen circumstances that would result in increased risk associated with completion of the protocol conduct for study patients, such as during natural disasters (floods, tornadoes, eart... | [
"Summary:"
] |
NCT04603495 | 11 | REFERENCES | 11. REFERENCES - Arber, D., Orazi, A., Hasserjian, R., Thiele, J., Borowitz, M. J., Le Beau, M. M., Bloomfield, C. D., Cazzola, M., & Vardiman, J. W. (2016). The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood, 127(20), 2391-2405. - Barosi G, Mesa RA, Thiele ... | [] |
NCT04620135 | 1 | INTRODUCTION | 1. INTRODUCTION | [] |
NCT04620135 | 1.1 | Investigational Product | 1.1 Investigational Product Glaucoma is a progressive optic neuropathy that causes characteristic loss of visual fields and can eventually lead to blindness. A major risk factor for glaucomatous visual field loss is elevated intraocular pressure (IOP) [\(AGIS 2000](#page-63-2)). The need for improved efficacy of glauco... | [] |
NCT04620135 | 1.2 | Findings from Non-Clinical and Clinical Studies | 1.2 Findings from Non-Clinical and Clinical Studies
Non-Clinical Proof of concept for netarsudil in lowering IOP was established in primary pharmacology studies in 2 species, rabbits and monkeys. Safety pharmacology (central nervous system, respiratory, and cardiovascular) of netarsudil was investigated in rats and do... | [
"Non-Clinical",
"Clinical"
] |
NCT04620135 | 1.3 | Risks and Benefits to Human Subjects | 1.3 Risks and Benefits to Human Subjects Netarsudil ophthalmic solution 0.02% was approved in the US on December 18, 2017 and in the EU and the UK on November 19, 2019 under the trade name of Rhopressa® and Rhokiinsa®, respectively. In the US Phase 3 studies, [AR-13324-CS301, AR-13324-CS302,](#page-65-0) and [AR-13324-... | [] |
NCT04620135 | 2 | STUDY OBJECTIVES | 2. STUDY OBJECTIVES | [] |
NCT04620135 | 2.1 | Primary Objective(s) | 2.1 Primary Objective(s) The objective of this study is: • To evaluate the ocular hypotensive efficacy and safety of netarsudil ophthalmic solution 0.02% QD compared to the active comparator, ripasudil hydrochloride hydrate ophthalmic solution 0.4% BID, over a 4-week period (superiority study). | [] |
NCT04620135 | 3 | INVESTIGATIONAL PLAN | 3. INVESTIGATIONAL PLAN Figure 1 Study Design  | [] |
NCT04620135 | 3.1 | Overall Study Design and Plan | 3.1 Overall Study Design and Plan This study will be a prospective, single-masked, randomized, multi-center, parallel-group, 4-week study evaluating the efficacy and safety of once daily (QD) netarsudil ophthalmic solution 0.02% compared to twice daily (BID) ripasudil hydrochloride hydrate ophthalmic solution 0.4% in J... | [] |
NCT04620135 | 3.2 | Rationale for Study Design and Control Group | 3.2 Rationale for Study Design and Control Group This is a randomized, single-masked, comparative study to confirm the superiority of netarsudil 0.02% QD to ripasudil hydrochloride hydrate ophthalmic solution 0.4% BID in patients with POAG or OHT. The primary efficacy endpoint of the study is mean diurnal IOP at Week 4... | [] |
NCT04620135 | 3.3 | Expected Duration of Subject Participation | 3.3 Expected Duration of Subject Participation Each subject is planned to undergo a minimum washout period of their current ocular hypotensive medications (if needed), followed by approximately 28 days of treatment. Treatment duration with the study drug for this study will start on the evening of Visit 3 (Qualificatio... | [] |
NCT04620135 | 4 | STUDY POPULATION SELECTION | 4. STUDY POPULATION SELECTION | [] |
NCT04620135 | 4.1 | Study Population | 4.1 Study Population A total of approximately 240 Japanese subjects will be enrolled in this study at approximately 28 investigational sites in Japan comprising a total of 120 subjects per treatment arm for each of the 2 treatment arms. Subjects will be at least 20 years of age with diagnosed POAG or OHT, each of whom ... | [] |
NCT04620135 | 4.2 | Inclusion Criteria | 4.2 Inclusion Criteria Subjects have to meet all of the following criteria at screening and qualification visits to enter into the study: - 1. 20 years of age or older - 2. Diagnosis of POAG or OHT in both eyes (POAG in one eye and OHT in the fellow eye is acceptable) - 3. Medicated intraocular pressure (IOP) ≥ 14 mmHg... | [] |
NCT04620135 | 4.3 | Exclusion Criteria | 4.3 Exclusion Criteria Subjects meeting any of the following criteria during screening or qualification evaluations (e.g., at the time of randomization) will be excluded from entry into the study:
Ophthalmic: - 1. Clinically significant ocular disease (e.g., corneal edema, uveitis, or severe keratoconjunctivitis sicca... | [
"Ophthalmic:",
"Systemic:"
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NCT04620135 | 5 | STUDY TREATMENTS | 5. STUDY TREATMENTS | [] |
NCT04620135 | 5.1 | Description of Treatments | 5.1 Description of Treatments | [] |
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